Inflammation Susceptibility in Eda Mutant, Tabby, Mice With Severe Ocular Surface Disease

Abstract

Abstract: : Purpose: To describe ocular surface abnormalities in mutant EDA tabby mice, a model of X–linked anhidrotic/hypohidrotic ectodermal dysplasia (EDA) and describe the ocular effects of the mEDA–A1 transgene. Methods: Fifty eyes from EDA mutant, Tabby mice, (27 males and 3 females), mEDA–A1 transgenic Tabby (4 males), WT transgenic mice (4 males), and wild–type controls (12 males), (4–45 weeks old) were examined. Mice were housed in a conventional facility with free access or a pathogen–free barrier facility. Gross and histology were performed and eyes with intact eyelids and conjunctiva were fixed in 10% buffered formalin and stained with hematoxylin and eosin. Results:Histology of eyes of Tabby males revealed that 1) as previously reported, meibomian glands were absent; 2) >80% developed cornea lesions including neovascularization, keratitis, ulceration and keratinization identifiable from 9 weeks of age; and 3) >80% showed ocular surface inflammation (blepharitis and conjunctivitis) when housed in a standard environment. Strikingly, in Tabby Eda–A1 transgenic mice, corneal defects and inflammation were both prevented, but meibomian glands were restored little if at all. 10/12 Tabby males housed in the conventional facility demonstrated dramatic ocular surface abnormalities: 5 blepharitis, 4 conjunctivitis, and 1 had both demonstrating a propensity for ocular inflammation which was apparently dependent on the environment in conventional housing. In contrast, 2/15 mice in pathogen–free facility demonstrated mild conjunctivitis only. Conclusions: Tabby and Tabby–EDA transgenic mice provide a unique model of severe ocular surface disease characterized by ulcer, neovascularization, keratitis and keratinization. Ocular surface health may be EDA–dependent and Tabby corneal abnormalities may not solely be dependent on meibomian gland lipid secretion. inflammation may result from the effect of the loss of EDA on the target NF–kB signal pathway.

Keywords: inflammation • conjunctiva • cornea: tears/tear film/dry eye